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. 2023 Aug 2:382:e074001.
doi: 10.1136/bmj-2022-074001.

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study

Victoria Hamill  1   2   3 , Stanley Wong  4   3 , Jennifer Benselin  5   6 , Mel Krajden  4   7 , Peter C Hayes  8 , David Mutimer  9 , Amanda Yu  4 , John F Dillon  10 , William Gelson  11 , Hector A Velásquez García  4   12 , Alan Yeung  1   2 , Philip Johnson  13 , Stephen T Barclay  14 , Maria Alvarez  4 , Hidenori Toyoda  15 , Kosh Agarwal  16 , Andrew Fraser  17   18 , Sofia Bartlett  4   7 , Mark Aldersley  19 , Andy Bathgate  8 , Mawuena Binka  4 , Paul Richardson  20 , Joanne R Morling  5   6   21 , Stephen D Ryder  5 , Douglas MacDonald  22 , Sharon Hutchinson  1   2 , Eleanor Barnes  23 , Indra Neil Guha  5   6 , William L Irving  5   6 , Naveed Z Janjua  4   12   24 , Hamish Innes  1   2   21
Affiliations

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study

Victoria Hamill et al. BMJ. .

Abstract

Objectives: To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population.

Design: Population based cohort study.

Setting: British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only).

Participants: 21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019.

Main outcome measures: Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates.

Results: 1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates.

Conclusion: Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Medical Research Foundation for the submitted work; the following financial relationships, which might have an interest in the submitted work in the previous three years: STB has received consulting fees and/or honorariums from Falk, Gilead, Abbvie, and Intercept; AB has received honorariums from Gilead Sciences; HT has received honorariums from Abbvie, Gilead Sciences, Eisai, Terumo, and Fujifilm WAKO; NZJ has received honorariums from Gilead and Abbvie; PCH has received honorariums from Falk, Ferring, Gore, Lundbeck, and Norgine; he has participated on advisory boards for Abbvie BMS, Eisai, Ferring, Gilead, Janssen, MSD, Novartis, and ONO; WLI has received research funding from Gilead Sciences and Jansen-Cilag and consulting fees/honorariums from Gilead Sciences and Roche Diagnostics; SB has received grants/contracts from Gilead Sciences and consulting fees/honorariums from Abbvie, Gilead Sciences; JFD has received honorariums from Gilead Sciences, Abbvie, and MSD; KA has received honorariums and/or consulting fees from Aligos, Assembly, Arbutus, BMS, BI, Bluejay, Gilead, GSK, Janssen, Roche, Saigmet, and Sobil; he has participated on the advisory board for DrugFarm; MA has received honorariums from Gilead Sciences; EB has consulted for Roche, Astrazeneca, and Vaccitech; she has received honorariums for education events and manuscript writing with Roche, and has patents relating to vaccines against hepatitis B, hepatitis C, and liver imaging; she owns shares in Perspectum diagnostics in liver imaging. No other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Number of people successfully treated for hepatitis C virus and number of deaths by setting and liver disease severity. ESLD=end stage liver disease
Fig 2
Fig 2
Crude and standardised all cause mortality rates by setting and liver disease severity. *Mortality rates are standardised for age and sex using patients from British Columbia (BC) as standard population; therefore, crude and standardised mortality rates for British Columbia are equal (see table S12 for further details). †Mortality data for people without cirrhosis (pre-cirrhosis) were not available for the England cohort. 95% CI=95% confidence interval
Fig 3
Fig 3
Standardised mortality ratio for all cause mortality by setting and liver disease severity. *Expected deaths indicates the number of deaths that would have occurred if people who had been successfully treated for hepatitis C had the same age-sex-year specific mortality rates as the corresponding general population. †Standardised mortality ratio is the ratio of observed to expected deaths; values >1 indicate excess mortality (number of observed deaths exceed number of expected deaths). ‡Null hypothesis is that standardised mortality ratio=1 (dashed line). §Mortality data for patients without cirrhosis (pre-cirrhosis) were not available for England cohort. 95% CI=95% confidence interval; BC=British Columbia
Fig 4
Fig 4
Cause specific contribution (%) to excess mortality by setting and liver disease severity. Excess mortality defined as number of observed deaths minus number of expected deaths (expected if the age-sex-year specific mortality rates in each cohort were identical to the corresponding general population). Total number of excess deaths for each setting and disease stage is given in brackets. Mortality data for patients without cirrhosis (pre-cirrhosis) were not available for England cohort. BC=British Columbia
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